Interferon regulatory factor�3 mediates Poly(I:C)-induced innate immune response and apoptosis in non‑small cell lung cancer

作者：Yi Liang, Dan Sun, Qian Han, Zhonghui Liu, Zeng Zeng, Yanping Wu, Xiaoyu Chai, Xinmin Liu · 发表于：International Journal of Oncology · 年份：2018 · DOI：10.3892/ijo.2018.4300 · 被引用次数：7 · 研究领域：interferon and immune responses、Immune Response and Inflammation、Immune Cell Function and Interaction

Immunotherapy is considered one of the most promising treatments for lung cancer. The cell signalling molecules melanoma differentiation-associated protein 5 (MDA5) and retinoic acid-inducible gene I protein (RIG‑I) are essential receptors that recognise intracellular pathogen-associated nucleic acids, whereas interferon regulatory factor 3 (IRF3) controls the expression of innate immunity-associated genes in macrophages. However, the innate immune response to polyinosinic:polycytidylic acid [Poly(I:C)] in lung cancer remains to be elucidated. In the present study, western blot analysis, reverse transcription-quantitative polymerase chain reaction, RNA interference, IRF3 plasmid construction, ELISA and apoptosis analysis were employed to study the innate immune response and apoptosis of non‑small cell lung cancer (NSCLC) cells. Poly(I:C) transfection in NSCLC cells triggered apoptosis via the extrinsic apoptotic pathway, and activated the innate immune response by promoting interferon-β and C-X-C motif chemokine ligand 10 expression. Treatment with the IκB kinase ε/tumour necrosis factor receptor-associated factor family member-associated nuclear factor-κB activator-binding kinase 1 inhibitor BX795, which inhibits IRF3 phosphorylation, or transfection with small interfering RNA/short hairpin RNA to downregulate MDA5, RIG‑I or IRF3, prior to Poly(I:C) transfection inhibited the innate immune response and apoptotic pathway. Conversely, IRF3 overexpression promoted activation of...